The invention relates to novel antihistaminic and antitussive tannate compositions. The compositions contain as essential ingredients carbetapentane tannate and pyrilamine tannate.
A considerable number of tannic acids occur in nature. Chemically, these acids are described as polymers of different hydroxybenzoic acids. Generally, when the term tannic acid is employed, as in the present case, the acid referred to is gallotannic acid, the internal ester of gallic acid also frequently referred to as tannin.
Tannic Acid consists of an amorphous powder glistening scales or spongy masses varying in color from yellowish-white to light brown. Tannic acid is very soluble in water, glycerine or alcohol.
Tannic acids are usually obtained from glycosides which consist of several molecules of a tannic acid in combination with glucose.
Commercially available, tannic acid, also known as Tannin, has a complex non-uniform chemistry usually contains from about 5% to about 10% by weight water, has a molecular weight of about 1700 and is typically produced from Turkish or Chinese nutgall.
Carbetapentane, 2-(2-diethylaminoethoxy)ethyl-1 phenylcyclopentane carboxlate is an antitussive compound that is described in U.S. Pat. No. 2,842,585 and is structurally related to caramiphen. Carbetapentane citrate has a melting point of 93xc2x0 C. and occurs as a white powder freely soluble in water and slightly soluble in alcohol.
Carbetapentane has an atropine-like action that depresses the cough reflex by selective central nervous system depression.
Pyrilamine is one of the oldest and most enduring antihistaminic drugs, known chemically as N-[(4-methoxyphenyl)methyl]-Nxe2x80x2,Nxe2x80x2-dimehthyl-N-2-pyridinyl-1,2-ethanediamine, its preparation is disclosed in U.S. Pat. No. 2,502,151 and is an oily liquid. Pyrilamines hydrochloride salt is very soluble in water and has a melting point of 143-143.5xc2x0 C. whereas the maleate salt is slightly soluble in water, benzene and ether and has a melting point of 100-101xc2x0 C.
Antihistamine compounds in the form of their free bases as well as their salts, e.g. hydrochloride, citrate, maleate, tannate, etc., are well known. Antihistamines in the form of their tannate salts are very desirable because such salts are generally stable and may be combined in such form without any untoward side effects.
Antihistaminics and antitussives in the form of their tannate salts are typically prepared by reacting the free base, e.g. pyrilamine, carbetapentane, etc. with tannic acid in the presence of a volatile solvent, usually isopropanol. Typically, in the conventional isopropanol route, the decongestant or antihistaminic free base and the tannic acid will be present in the isopropanol at a concentration of about 20% based on the weight of the reaction mixture. The reaction mixture is stirred for about one hour while maintaining the mixture at 60-70xc2x0 C. The reaction mixture is cooled to room temperature and then filtered, washed with isopropanol and then vacuum dried. Alternative routes to the tannate salts are described in U.S. Pat. Nos. 5,599,846 and 5,663,415.
It has now been found that the novel combination of carbetapentane tannate and pyrilamine tannate produces a composition having antitussive and antihistaminic properties superior to the use of either one of the tannate compounds alone.
The compositions of the present invention may be prepared for oral administration in the form of powders, capsules, elixirs, syrups and the preferred forms of tablets formulated so that ideally each tablet contains about 50 mg to about 75 mg, preferably about 60 mg of carbetapentane tannate and about 50 mg to about 75 mg, preferably about 60 mg pyrilamine tannate or suspensions formulated so that ideally each 5 mL (approximately 1 teaspoon) of suspension would contain approximately 20 to 30 mg carbetapentane tannate and an equal amount of pyrilamine tannate.
Tablets containing the unique tannate combination of the present invention are prepared in a conventional manner by the addition of suitable pharmaceutical carriers including fillers, diluents, colorants, lubricants and the like as well as conventional and well known binding and disintegrating agents. A typical tablet composition of the present invention containing starch, dibasic calcium phosphate, coloring, magnesium stearate, methylcellulose, polygalacturoic acid, povidone and talc as described in Example 1 which follows is prepared by well known conventional tabletting techniques such as those disclosed in U.S. Pat. Nos. 3,018,221; 2,798,024 and 2,757,124.